P1124: MOSUNETUZUMAB RETREATMENT IS EFFECTIVE AND WELL-TOLERATED IN PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN LYMPHOMA
Authors: C. Y. Cheah, N. L. Bartlett, S. Assouline, S. J. Schuster, W. Seog Kim, M. Shadman, I. Isufi, S. Yin, M. Y. Doral, J. Sit, V. Chen, H. Huang, M. Zhou, M. C. Wei, L. E. Budde
Journal: HemaSphere (2022)

Background: The prognosis for heavily pretreated patients (pts) with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) is poor and there is a need for effective treatment options (Batlevi, et al. 2020; Crump, et al. 2017). Mosunetuzumab (M) is a T-cell engaging CD20xCD3 bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells (Sun, et al. 2015; Budde, et al. 2022). Results from a single-arm, Phase I/II study (NCT02500407) of M in pts with R/R aggressive and indolent NHL showed durable complete responses (CR) and a manageable safety profile (Budde, et al. 2022). Specifically, in pts with R/R follicular lymphoma (FL) after ≥2 prior therapies, M demonstrated a 60% CR rate and an 80% objective response rate with a median duration of response (DoR) of 22.8 months (Budde, et al. ASH 2021). Initial M treatment had a fixed duration (8 cycles for pts who achieved CR; 17 cycles for pts with partial response or stable disease after 8 cycles); however, for pts who achieved a CR but had progressive disease (PD) after initial treatment completion, M retreatment could be provided. We report additional data from this ongoing study to describe the M retreatment experience of pts with R/R NHL. Aims: To evaluate the efficacy and safety of M monotherapy (mono) retreatment in pts with R/R NHL from an ongoing Phase I/II study (NCT02500407). Methods: Pts with R/R NHL who achieved CR after initial treatment with intravenous (IV) M mono but subsequently developed PD after treatment completion were eligible for retreatment. Pts were retreated with IV M mono at a previously tested dose and schedule, which included step-up dosing for cytokine release syndrome (CRS) mitigation. All pts provided informed consent. Results: At the clinical cut-off date, March 15, 2021, 12 pts received M retreatment; 6 pts completed retreatment and 6 pts discontinued retreatment (PD, n=5; start of another anti-lymphoma therapy, n=1). M retreatment step-up dose schedules were as follows (Cycle [C] 1, Day [D] 1/C1D8/C1D15/C2D1/C3+D1): 1/2/13.5mg (n=1), 1/2/20mg (n=1), 1/2/27mg (n=1), 1/2/40.5mg (n=1) and 1/2/60/60/30mg (n=8). Median number of M retreatment cycles received was 8.0 (range, 2–13). Overall, 8 pts with R/R FL, 2 pts with R/R diffuse large B-cell lymphoma (DLBCL), 1 pt with R/R transformed FL (trFL) and 1 pt with R/R mantle cell lymphoma (MCL) were included in the analysis. During retreatment, 9 (75.0%) pts had an objective response (6/8 pts with R/R FL; 2/2 pts with R/R DLBCL; 1/1 pt with trFL; and 0/1 pt with MCL; Table). Six/12 pts achieved a CR (4/8 pts with R/R FL, 1/2 pts with R/R DLBCL; 1/1 pt with R/R trFL; and 0/1 pt with MCL). All pts who received M retreatment were included in the safety population and had ≥1 adverse event (AE). The most common any-grade AE and Grade 3–4 AE was hypophosphatemia (n=7, 58.3% [each]; none were serious and all events resolved with or without treatment). Four pts experienced ≥1 serious AE. No Grade 5 events were reported and no pts had an AE that led to treatment discontinuation. Three pts (25.0%) had low-grade CRS (by Lee, 2014; Grade 1, n=2; Grade 2, n=1) and there were no Grade 3–4 CRS events. Image:Summary/Conclusion: Our results show that IV M mono retreatment was efficacious in heavily pretreated pts with R/R NHL who initially achieved a CR with M treatment, but subsequently developed PD. M retreatment had a manageable safety profile, consistent with the initial treatment.